Nuclear import of aristaless-related homeobox protein via its NLS1 regulates its transcriptional function

作者：Ye Wenduo; Lin Wenbo; Tartakoff Alan M; Ma Qilin; Tao Tao^*

来源：Molecular and Cellular Biochemistry, 2013, 381(1-2): 221-231.

DOI：10.1007/s11010-013-1706-7

• Arx
• Importin alpha/beta
• Nuclear localization signal
• Transcriptional repression

Nucleocytoplasmic transport of transcription factors is essential in eukaryotes. We previously reported the presence of two functional NLSs in the homeodomain protein, aristaless-related homeobox (Arx) protein, which is a key transcriptional repressor of LMO1, SHOX2, and PAX4 during development. NLS2, that overlaps the homeodomain, is recognized directly by multiple importin beta s, but not by importin alpha s. In this study, we found that the N-terminal NLS1 of Arx is targeted by multiple importin alpha proteins, including importin alpha 3 and alpha 5. Both in vivo and in vitro assays demonstrated that nuclear import of Arx via NLS1 is mediated by the importin alpha/beta pathway. Mutagenesis analysis indicated that two basic amino acids, K-84 and R-87, are essential to the function of NLS1, and that their mutation prevents interactions of Arx with importin alpha s. Interestingly, inhibition of nuclear import of Arx via NLS1 clearly attenuates its ability of transcriptional repression, suggesting that nuclear import of Arx via NLS1 contributes to its transcriptional function.

• 出版日期2013-9
• 单位厦门大学